The provirus of the Moloney murine sarcoma virus (MSV) contains both an MSV- specific transforming sequence (v-mos) and sequences [the MSV long terminal repeat (LTR)] which contain presumptive promoters for activation of RNA synthesis. The LTR acts to enhance v-mos transformation when linked either 5' or 3' relative to v-mos, and analysis of polyadenylated RNA indicates RNA synthesis either initiates or terminates in the LTR, depending on its location relative to mos. LTR-containing DNA clones also enhance v-mos transformation when two separate fragments are co-precipitated and co-transfected. We have developed a screening and selection system to identify dominant transforming DNA sequences based on the ability of NIH 3T3 cells transfected by such sequences to induce tumors in athymic nude mice. Under appropriate conditions this assay is as sensitive as conventional focus assays in tissue culture. Transfected sequences are present in tumors and virus can be rescued or viral antigens detected in cell lines derived from tumor explants. We have presently identified three human tumor DNAs capable of inducing tumors in our assay. We have also studied the genetics and biochemistry of ts-110, an MSV temperature-sensitive (ts) deletion mutant, which transforms cells at 34 but not at 39 degrees.